Abstract

PURPOSE: Severe Sepsis (SS) is associated with acute organ dysfunction. An abnormal activation of the coagulation system may result in a thrombotic obstruction of the microvasculature, and contribute to the pathogenesis of organ failure. This procoagulant state can cause a consumption coagulopathy and the formation of microthrombi in small vessels; thereby disrupting blood flow. Even with stable systemic hemodynamics, the compromised microcirculation may contribute to regional hypoxia, and cause multiple organ failure (MOF). SS is also characterized by a concurrent inhibition of physiologic anticoagulant mechanisms. Activation of the coagulation system leads to an increased consumption of Protein-C(PC) and Antithrombin-III(AT-III), augmenting the procoagulant state.

METHODS: 50 patients hospitalized in the ICU with a diagnosis of sepsis were included. They were screened for these variables: 1-All cause mortality during hospitalization, 2-Number of organs showing acute dysfunction, 3-Intubation and Assisted-Ventilation (IAV), 4-Vasopressor-Agents (VA), 5-Serial dosage of PC and AT-III, 6-Sites of infections.

RESULTS: All cause mortality was 50% (25/50). 94% (47/50) developed SS, with an average of 4.3 dysfunctional organs per patient. IAV was required in 80% of patients (40/50), and VA in 72% (36/50). A fall in PC was observed in 85% of patients with SS (40/47), and in 88% of the ones who died (22/25). Values of PC averaged 0.71UN/l (Normal: 0.63–1.22) in patients with no organ dysfunction (n=3), and 0.42UN/l in patients with SS (n=47). A fall in AT-III was seen in 93% of patients with SS (42/45), and in 95% of the ones who died (21/22). Values of AT-III averaged 0.45UN/l (Normal: 0.78–1.34) in patients with SS (n=45). A significant decrease in platelets was documented in 53% of patients with SS (25/47).

CLINICAL IMPLICATIONS: Microcirculatory dysfunction has a key role in the pathophysiology of SS and MOF. Early identification of patients at risk of microthrombosis is essential. Thus, reliable markers are definitely needed. Presently, the only criteria of acute hematological dysfunction (e.g. for giving Drotrecogin-Alfa) is based on the platelet count. Among our patients with SS, more individuals showed a drop in PC (85%) and AT-III (93%) than a fall in platelets (53%). Decreases in PC and AT-III may also occur earlier than the reduction in the platelets, rending these natural anticoagulants useful markers in the evaluation of the septic patient.

Return to: LOW LEVELS OF PROTEIN C AND ANTITHROMBIN III COULD SUGGEST THE PRESENCE OF MICROCIRCULATORY DYSFUNCTION AND PREDICT THE SEVERITY OF SEPSIS AND THE APPEARANCE OF MULTIPLE ORGAN FAILURE

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